ArticleProceedings of the National Academy of Sciences of the United States of America2005
Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- When copper turns killer: Decoding copper dyshomeostasis and cuproptosis in neurodegenerative pathogenesis and precision metal interventions.Neural regeneration research · 2026Article
- Targeting Copper in Cancer: Chelators to Counteract Cuproplasia and Ionophores to Promote Cuproptosis.Journal of medicinal chemistry · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Copper homeostasis and cuproptosis: implications for neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- New applications of clioquinol in the treatment of inflammation disease by directly targeting arginine 335 of NLRP3.Journal of pharmaceutical analysis · 2025Article
- Copper homeostasis and cuproptosis in central nervous system diseases.Cell death & disease · 2024Review
- Article
- Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.Neuroprotection (Chichester, England) · 2024Article
- Bioinformatics and systems biology approaches to identify the effects of COVID-19 on neurodegenerative diseases: A review.Medicine · 2022Review
- The Zinc Ionophore Clioquinol Reduces Parkinson's Disease Patient-Derived Brain Extracts-Induced Neurodegeneration.Molecular neurobiology · 2022Article
- Identification of 8-Hydroxyquinoline Derivatives That Decrease Cystathionine Beta Synthase (CBS) Activity.International journal of molecular sciences · 2022Article
- Mitochondrial iron metabolism and neurodegenerative diseases.Neurotoxicology · 2022Review
- Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Copper(II) Binding to PBT2 Differs from That of Other 8-Hydroxyquinoline Chelators: Implications for the Treatment of Neurodegenerative Protein Misfolding Diseases.Inorganic chemistry · 2020Article
- Prolongation of metallothionein induction combats Aß and α-synuclein toxicity in aged transgenic Caenorhabditis elegans.Scientific reports · 2020Article
- Article
- A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A.ACS chemical biology · 2019Article
- iNKT Cell Activation Exacerbates the Development of Huntington's Disease in R6/2 Transgenic Mice.Mediators of inflammation · 2019Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates. Clioquinol treatment of transgenic Huntington's mice (R6/2) improved behavioral and pathologic phenotypes, including decreased huntingtin aggregate accumulation, decreased striatal atrophy, improved rotarod performance, reduction of weight loss, normalization of blood glucose and insulin levels, and extension of lifespan. Our results suggest that clioquinol is a candidate therapy for Huntington's disease and other polyglutamine-expansion diseases.
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